Business in the Borderlands: Bent, St. Vrain & Co., 1830-1849

During the 1830s and 1840s, a unique set of economic, social, political, and environmental factors contributed to the rise and fall of Bent, St. Vrain & Co. as the preeminent American trading firm in the Southwest Borderlands. Between the company\'s founding around 1830 and the destruction of Bent\'s Fort in 1849, the Bent brothers and Ceran St. Vrain conducted a wide-ranging, multifaceted trade with the United States, Mexico, and the Native American tribes of the Southern Plains. Geographical and political isolation made it imperative for the partners to adhere to a strict set of social and economic protocols, especially the cultivation of business patronage and intermarriage with their clients. The most important factor in the company\'s strategy was the weak presence of the State - either American or Mexican - in the borderlands. The weakness of the State simultaneously presented the partners with both opportunities and challenges. On the one hand, they were in a precarious position - unable to call upon the American government for protection, they went out of their way to avoid alienating the powerful tribes of the region. On the other hand, the weakness of the Mexican State allowed the Bents and St. Vrain to circumvent national trade laws, become smugglers, and acquire land grants, all of which alienated the nationalist faction in New Mexico. The arrival of the American State in the borderlands in 1846 set in motion a chain of events that ultimately brought down the company. The conquest of New Mexico unleashed a wave of violence that destroyed the conditions that had allowed the partners to prosper. By 1849, Bent\'s Fort - the symbol of company power - went up in flames, abandoned by its proprietors. Far from the centers of State power, Bent, St. Vrain & Co. flourished for nearly two decades. American expansion rendered the company\'s position within the borderlands untenable

Middle-Class Masculinity and the Klondike Gold Rush

Social theorists in the late nineteenth-century identified two ideals of masculinity. The first type emphasized financial responsibility and familial duties like breadwinning and child-rearing, as well as Christian living. Most writers who adhered to this ideal cautioned middle-class men against going to the Klondike. Critics stressed the fact that there was no guarantee men would become rich. Opponents wrote that the trip was difficult. They argued that if men did go they should not forsake their religious responsibilities and obligations. Some writers pointed out that the trip represented an abrogation of domestic duties. The second ideal stressed aggressive, self-assertive behavior. Proponents urged men to get out of the cities and into the wilderness. If men were in good physical shape and possessed steady nerves the trip would be positively beneficial. In the gold camps men might also take part in "male" activities like drinking and gambling.Department of Histor

Deregulated microRNAs in biliary tract cancer: functional targets and potential biomarkers

Biliary tract cancer (BTC) is still a fatal disease with very poor prognosis. The lack of reliable biomarkers for early diagnosis and of effective therapeutic targets is a major demanding problem in diagnosis and management of BTC. Due to the clinically silent and asymptomatic characteristics of the tumor, most patients are diagnosed at an already advanced stage allowing only for a palliative therapeutic approach. MicroRNAs are small noncoding RNAs well known to regulate various cellular functions and pathologic events including the formation and progression of cancer. Over the last years, several studies have shed light on the role of microRNAs in BTC, making them potentially attractive therapeutic targets and candidates as biomarkers. In this review, we will focus on the role of oncogenic and tumor suppressor microRNAs and their direct targets in BTC. Furthermore, we summarize and discuss data that evaluate the diagnostic power of deregulated microRNAs as possible future biomarkers for BTC

Deregulated MicroRNAs in Biliary Tract Cancer: Functional Targets and Potential Biomarkers

Biliary tract cancer (BTC) is still a fatal disease with very poor prognosis. The lack of reliable biomarkers for early diagnosis and of effective therapeutic targets is a major demanding problem in diagnosis and management of BTC. Due to the clinically silent and asymptomatic characteristics of the tumor, most patients are diagnosed at an already advanced stage allowing only for a palliative therapeutic approach. MicroRNAs are small noncoding RNAs well known to regulate various cellular functions and pathologic events including the formation and progression of cancer. Over the last years, several studies have shed light on the role of microRNAs in BTC, making them potentially attractive therapeutic targets and candidates as biomarkers. In this review, we will focus on the role of oncogenic and tumor suppressor microRNAs and their direct targets in BTC. Furthermore, we summarize and discuss data that evaluate the diagnostic power of deregulated microRNAs as possible future biomarkers for BTC

In Vitro Cell Death Discrimination and Screening Method by Simple and Cost-Effective Viability Analysis

Background/Aims: For in vitro cytotoxicity testing, discrimination of apoptosis and necrosis represents valuable information. Viability analysis performed at two different time points post treatment could serve such a purpose because the dynamics of metabolic activity of apoptotic and necrotic cells is different, i.e. a more rapid decline of cellular metabolism during necrosis whereas cellular metabolism is maintained during the entire execution phase of apoptosis. This study describes a straightforward approach to distinguish apoptosis and necrosis. Methods: A431 human epidermoid carcinoma cells were treated with different concentrations/doses of actinomycin D (Act-D), 4,5,6,7-tetrabromo-2-azabenzimidazole (TBB), Ro 31-8220, H2O2 and photodynamic treatment (PDT). The resazurin viability signal was recorded at 2 and 24 hrs post treatment. Apoptosis and necrosis were verified by measuring caspase 3/7 and membrane integrity. Results: Calculation of the difference curve between the 2 and 24 hrs resazurin signals yields the following information: a positive difference signal indicates apoptosis (i.e. high metabolic activity at early time points and low signal at 24 hrs post treatment) while an early reduction of the viability signal indicates necrosis. For all treatments, this dose-dependent sequence of cellular responses could be confirmed by independent assays. Conclusion: Simple and cost-effective viability analysis provides reliable information about the dose ranges of a cytotoxic agent where apoptosis or necrosis occurs. This may serve as a starting point for further in-depth characterisation of cytotoxic treatments

International Journal of Molecular Sciences / Acid- and Volume-Sensitive Chloride Currents in Microglial Cells

Many cell types express an acid-sensitive outwardly rectifying (ASOR) anion current of an unknown function. We characterized such a current in BV-2 microglial cells and then studied its interrelation with the volume-sensitive outwardly rectifying (VSOR) Cl current and the effect of acidosis on cell volume regulation. We used patch clamp, the Coulter method, and the pH-sensitive dye BCECF to measure Cl currents and cell membrane potentials, mean cell volume, and intracellular pH, respectively. The ASOR current activated at pH 5.0 and displayed an I > Cl > gluconate permeability sequence. When compared to the VSOR current, it was similarly sensitive to DIDS, but less sensitive to DCPIB, and insensitive to tamoxifen. Under acidic conditions, the ASOR current was the dominating Cl conductance, while the VSOR current was apparently inactivated. Acidification caused cell swelling under isotonic conditions and prevented the regulatory volume decrease under hypotonicity. We conclude that acidification, associated with activation of the ASOR- and inactivation of the VSOR current, massively impairs cell volume homeostasis. ASOR current activation could affect microglial function under acidotoxic conditions, since acidosis is a hallmark of pathophysiological events like inflammation, stroke or ischemia and migration and phagocytosis in microglial cells are closely related to cell volume regulation.(VLID)435620